依霉素单抗与非蒽环类化疗免疫治疗在新诊断的高心血管风险弥漫性大b细胞淋巴瘤患者中的匹配调整比较

IF 3.9 4区医学 Q2 HEMATOLOGY

Hematological Oncology Pub Date : 2025-06-16 DOI:10.1002/hon.70094_291

P. C. Johnson, E. Guo, G. Zhang, T. Wang, V. Patel, A. Mutebi, M. Atiya, J. Ukropec, A. Wang, S. Diness Vindeløv, J. Darrah

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This analysis compares the efficacy of epcor mono versus non-AC CIT in pts with newly diagnosed DLBCL and HRCV status.Methods: Individual pt data for first-line (1L) epcor from the EPCORE DLBCL-3 trial were compared with pts treated with 1L non-AC CIT in the real-world setting. Pts diagnosed with DLBCL from 2007–2017 were identified from the US National Cancer Institute Surveillance, Epidemiology, and End Results database for initial diagnosis records and linked to the US Medicare database for treatment details using diagnosis codes (ICD-O-3: 9680/9688). Non-AC CITs included R-CVP (rituximab, cyclophosphamide, vincristine sulfate, and prednisone) or R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and oral prednisolone) and BR (bendamustine and rituximab). HRCV status was defined using the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology criteria (Lyon AR et al. 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引用次数: 0

摘要

含蒽环类药物（AC）化学免疫治疗（CIT）方案可能不适合新诊断的弥漫性大b细胞淋巴瘤（DLBCL）患者（患者），年龄较大和/或有特定的合共病，因为心血管毒性的风险增加。在EPCORE DLBCL-3 （NCT05660967）试验中，epcoritamab （epcor）单药治疗（mono）在新诊断的DLBCL和HRCV状态的患者中显示出良好的疗效和可管理的安全性（Morschhauser等）。血。2024;144:867)。该分析比较了单抗epcor与非ac CIT在新诊断的DLBCL和HRCV状态的患者中的疗效。方法：将来自EPCORE DLBCL-3试验的一线（1L） epcor的个体pt数据与现实环境中使用1L非ac CIT治疗的患者进行比较。2007-2017年诊断为DLBCL的患者从美国国家癌症研究所监测、流行病学和最终结果数据库中确定初始诊断记录，并使用诊断代码（ICD-O-3: 9680/9688）链接到美国医疗保险数据库以获取治疗细节。非ac CITs包括R-CVP（利妥昔单抗、环磷酰胺、硫酸长春新碱和强的松）或R-CEOP（利妥昔单抗、环磷酰胺、依托泊苷、长春新碱和口服强的松龙）和BR（苯达莫司汀和利妥昔单抗）。HRCV状态是根据欧洲心脏病学会心力衰竭协会心脏肿瘤学研究组的标准定义的（Lyon AR等）。[J]心力衰竭2020；22:45)，并基于年龄和/或合并症的存在，包括心力衰竭、瓣膜疾病、心肌梗死、冠状动脉血运重建术、高血压、糖尿病或肾脏疾病。使用治疗加权逆概率来平衡治疗队列的关键可用变量：年龄、性别、安娜堡分期、HRCV评分和诊断后治疗时间。主要终点是总生存期（OS）。采用加权Cox回归模型估计风险比（hr）；时间-事件Kaplan-Meier曲线采用log-rank检验进行比较。结果：非ac CIT治疗81例，epcor治疗45例。调整前，epcor队列的女性患者较少（60.0% vs. 70.4%），年龄≥80岁的患者较少（82.2% vs. 95.1%）， Ann Arbor期患者较少（66.7% vs. 72.8%），平均HRCV评分较低（7.0 vs. 8.4）。与非ac CIT组相比，epcor组调整后的OS（中位OS不可评估）显著改善(中位OS 10.2；Hr 0.30 [95% ci: 0.14-0.66；P = 0.0027])。非ac CIT方案的亚组分析一致：epcor与R-CVP/R-CEOP (HR 0.34 [95% CI: 0.16-0.74]；p = 0.0067])和epcor vs BR (HR 0.21 [95% CI: 0.08-0.56]；p = 0.0019)（图A-C）。结论：在HRCV状态的DLBCL的1L治疗中，与非ac CIT相比，单药epcor显着改善了OS，这些发现突出了这一人群对新型无化疗治疗方案的关键需求。研究经费声明：本研究由Genmab A/S和AbbVie资助。关键词：非霍奇金潜在利益冲突来源；顾问或顾问角色：AbbVie、ADC Therapeutics、AstraZeneca、Bristol Myers Squibb、Incyte和SeagenOther薪酬：研究经费：AstraZeneca、medical Home、Novartis和onternale。任职或领导职务：GenmabG股份：GenmabG工作或领导职务：GenmabT股份：GenmabT工作或领导职务：GenmabV.股份：GenmabV.任职或领导职务：genmab股份：GenmabA就业或领导职位：GenmabM股份：GenmabM。工作或领导职务：GenmabJ.股份：GenmabJ.乌克兰就业或领导职位：genmabab股份：genmababa工作或领导职务：abbvie股份：abbvie任职或领导职务：GenmabJ.股份：GenmabJ.顾问或顾问角色：Kite和MorphoSys

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MATCH-ADJUSTED COMPARISON OF EPCORITAMAB VERSUS NON-ANTHRACYCLINE CHEMOIMMUNOTHERAPY IN NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS WITH HIGH CARDIOVASCULAR RISK

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MATCH-ADJUSTED COMPARISON OF EPCORITAMAB VERSUS NON-ANTHRACYCLINE CHEMOIMMUNOTHERAPY IN NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS WITH HIGH CARDIOVASCULAR RISK

Introduction: Anthracycline-containing (AC) chemoimmunotherapy (CIT) regimens may be unsuitable for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who are older and/or have specific comorbidities, due to elevated risk of cardiovascular toxicities. Consequently, pts with high-risk cardiovascular (HRCV) status are often treated with non-AC CIT. In the EPCORE DLBCL-3 (NCT05660967) trial, epcoritamab (epcor) monotherapy (mono) showed promising efficacy and manageable safety in pts with newly diagnosed DLBCL and HRCV status (Morschhauser F et al. Blood. 2024;144:867). This analysis compares the efficacy of epcor mono versus non-AC CIT in pts with newly diagnosed DLBCL and HRCV status.

Methods: Individual pt data for first-line (1L) epcor from the EPCORE DLBCL-3 trial were compared with pts treated with 1L non-AC CIT in the real-world setting. Pts diagnosed with DLBCL from 2007–2017 were identified from the US National Cancer Institute Surveillance, Epidemiology, and End Results database for initial diagnosis records and linked to the US Medicare database for treatment details using diagnosis codes (ICD-O-3: 9680/9688). Non-AC CITs included R-CVP (rituximab, cyclophosphamide, vincristine sulfate, and prednisone) or R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and oral prednisolone) and BR (bendamustine and rituximab). HRCV status was defined using the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology criteria (Lyon AR et al. Eur J Heart Fail 2020;22:1945) and based on age and/or presence of comorbidities, including heart failure, valvular disease, myocardial infarction, coronary revascularization, hypertension, diabetes, or kidney disease. Inverse probability of treatment weighting was used to balance treatment cohorts on key available variables: age, gender, Ann Arbor stage, HRCV score, and postdiagnosis time-to-treatment. The primary endpoint was overall survival (OS). Hazard ratios (HRs) were estimated by weighted Cox regression models; time-to-event Kaplan-Meier curves were compared using log-rank tests.

Results: Eighty-one pts receiving non-AC CIT and 45 receiving epcor were included. Before adjustment, the epcor cohort had fewer females (60.0% vs. 70.4%), fewer pts aged ≥ 80 years (82.2% vs. 95.1%), fewer pts with Ann Arbor stage III/IV (66.7% vs. 72.8%), and lower mean HRCV score (7.0 vs. 8.4). Adjusted OS was significantly improved in epcor (median OS not evaluable) versus non-AC CIT cohorts (median OS 10.2; HR 0.30 [95% CI: 0.14–0.66; p = 0.0027]). Subgroup analyses were consistent for non-AC CIT regimens: epcor versus R-CVP/R-CEOP (HR 0.34 [95% CI: 0.16–0.74]; p = 0.0067]) and epcor versus BR (HR 0.21 [95% CI: 0.08–0.56]; p = 0.0019) (Figures A–C).

Conclusions: In the 1L treatment of DLBCL with HRCV status, epcor mono demonstrated significantly improved OS versus non-AC CIT. These findings highlight a critical unmet need for novel chemotherapy-free treatment options in this population.

Research funding declaration: This study was funded by Genmab A/S and AbbVie.

Keywords: Non-Hodgkin

Potential sources of conflict of interest:

P. C. Johnson

Consultant or advisory role: AbbVie, ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Incyte, and Seagen

Other remuneration: Research funding: AstraZeneca, Medically Home, Novartis, and Oncternal

E. Guo